Experience induced increases in glucose and monosodium glutamate (MSG) taste sensitivity have been shown, and data suggest a peripheral nervous system (PNS) mechanism, perhaps in or before the receptor cells. Preliminary data are consistent with a hypothesis that allosteric modulation and/or cooperative binding of sweet and umami receptor molecules mediated by the receptor subunit, T1R3, may be a mechanism in the induction process. T1R3 is found in both sweet and umami receptors. This proposal is for (a) mouse behavioral studies to test the locus of the induction and (b) human psychophysical studies to test the hypothesis of a role for T1R3 in the induction. The long term objectives are to (a) better understand the taste induction process and (b) contribute to an understanding of taste PNS and receptor mechanisms. First, behavioral studies will test a prediction that experience with MSG will increase glucose sensitivity, and experience with glucose will increase MSG sensitivity in wildtype, but not in T1R3 knockout mice. Second, human psychophysical studies will test the prediction that experience with Na-cyclamate, which binds to T1R3, will induce changes in discrimination of MSG, an umami stimulus. Finally psychophysical studies will test the prediction that experience with Na-cyclamate should generalize, i.e. should induce increased discrimination for other sweeteners and umami stimuli. These studies should provide the first definitive evidence for experience induced plasticity in the PNS and are expected to support the hypothesis about a role for T1R3 in the induction. They should contribute significantly to an understanding of PNS and receptor mechanisms. The results could lead to development of novel strategies for compliance in the prevention and maintenance of obesity and nutrition related diseases. PUBLIC HEALTH RELEVANCE: Taste, especially sweet taste, is importantly related to two major public health problems-- the etiology and management of obesity and nutrition related diseases and the limited compliance of individuals to known prevention and management measures. These studies will provide information about the role of experience in sweet taste sensitivity and contribute to an understanding of nervous system and receptor mechanisms in sweet taste. The results may lead to the development of novel strategies for compliance to prevention and management measures and contribute to the development of acceptable non-caloric sweeteners, sweet antagonists, palatable medications and healthy foods which are palatable.